Pharmaceutical Sciences
Volume:14 Issue: 1, 2008

In spite of the increasing usage of herbal medicine in Iran, considerable research on their contaminations has not been carried out yet. Herbal medicines have been reported to contain many health hazards for herbal therapy patients. For this group, one of the health hazards is contamination to heavy metals such as Cadmium (Cd), Mercury (Hg) and Lead (Pb). Therefore, the aims of this study were the measurements of the level of Cd, Hg and Pb in oral herbal drops available in Iranian market. 10 different herbal products were purchased from market. A certain volume of each samples were digested with nitric acid by wet digestion method, then the final solutions of digestion were used to determine the contamination level of Cd, Hg and Pb. The measurements of Pb, Cd and Hg were performed by spectrometry of flame atomic absorption (AA), graphite furnace atomic absorption (GFAA) and cold vapor atomic absorption, respectively. The lead, cadmium and mercury contents in the investigated samples were found at different levels. Lead and cadmium were present in the majority of samples while mercury was detected on 3 of 10 samples. By a comparison between acceptable global standards and the level of cadmium, lead and mercury on investigated herbal medicines, our results showed that the quantities of these heavy metals were well below acceptable intake recommended by global standards. However, risk assessments needs considerable attention for herbal therapy patients on illness who may be more susceptible to these toxic elements.

Microencapsulation is a well-known method that is used to modify and retard drug release. In this study, the preparation of diclofenac sodium and Eudragit RS and/ or RL microcapsules was accomplished in order to asses the suitability of them for production of oral sustained release multiparticulate dosage form of diclofenac sodium. Microcapsules were prepared using the emulsion solvent evaporation method. The effect of formulation variables namely polymer:drug ratio, type of polymer and inclusion of PEG 400 as a channeling agent were investigated on shape and surface characteristics of microcapsules (by scanning electron microscopy), percentage yield and drug entrapment efficiency, mean particle size (sieve analysis) and drug release profiles (dissolution test). Microscopic examination of microcapsules revealed that all microcapsules were well-shaped and nearly spherical. Percentage yield was more than 90% and drug entrapment efficiency was more than 95% for most of the cases and therefore confirmed the suitability of the method for production of microcapsules with high drug loading. The mean particle size for different microcapsules was in the range of 390 - 589 μm. Drug release was very slow from microcapsules with 3:1 polymer: drug ratio. Increase in stirring speed did not influence the size and release characteristics of microcapsules at 3:1 polymer: drug ratio. Decrease in polymer:drug ratio to 2:1 did not significantly influence the release rate of drug. Further decrease in polymer: drug ratio to 1:1 increased the rate of drug release. However drug release from all formulations was incomplete at the end of dissolution test. Despite the higher water permeability of Eudragit RL both Eudragit types behaved similarly in controlling drug release rate. This observation and also incomplete drug release from all microcapsules were attributed to the probable electrostatic interaction between cationic quaternary ammonium groups in Eudragit RS and RL and diclofenac sodium.The inclusion of 10 or 20% PEG 400 in microcapsule wall resulted in microcapsules with very smooth surface and increased the rate of drug release. Calculation of difference factor revealed that the release profile of microcapsules with 1:1 polymer: drug ratio and containing 10% PEG was similar to commercial sustained release pellets of diclofenac sodium (Modafen). The emulsion solvent evaporation method was successful in production of diclofenac sodium and Eudragit RS or RL microcapsules. The yields of preparation and drug entrapment efficiencies were high for all microcapsules obtained. The drug: polymer ratio and inclusion of PEG 400 influenced the in vitro drug release; however the microencapsulation yield and drug entrapment efficiency were not influenced. The 1:1 polymer: drug ratio produced better release profile for oral drug delivery.

Several studies indicate that dopaminergic system has important role on morphine induced dependence and withdrawal syndrome.The aim of this study was to evaluate possible role of D2 receptor- by using bromocriptine and sulpiride (respectively agonist and antagonist of this receptor)- on morphine induced dependence and withdrawal signs. Experiments were performed on 17 groups (n=8) of adult male mice weighing between 20 and 25 g. Animals received saline (10 ml/kg, i.p.) or vehicle of drugs (DMSO 7% v/v + distilled water- 10 ml/kg, i.p.) or morphine (50 mg/kg, i.p.) or morphine with bromocriptine or sulpiride (10, 20, 40 mg/kg, i.p.) or morphine with both of drugs (bromocriptine and sulpiride). For evaluating of morphine dependence, animals received drugs one hour after morphine injection for six days. In order to assay of withdrawal symptoms drugs were injected only on the last day of morphine administration (6th day). For induction of withdrawal syndrome, naloxone (4 mg/kg, i.p.) was injected two hours after morphine injection on the last day and withdrawal signs (jumping and standing on feet) were evaluated for 30 minutes after naloxone injection. The results showed that bromocriptine has developed the morphine dependence and withdrawal syndrome significantly (p<0.05) but sulpiride only affected on number of standing on feet in dependence test study significantly (p<0.05) furthermore coadministration of bromocriptine and sulpiride could not affect on morphine dependence but increased the number of jumping in withdrawal syndrome study significantly (p<0.05). D2 receptors of dopaminergic system have a main role in morphine dependence and withdrawal syndrome but there are controversial results and the final effect of D2 agonists and antagonists administration remain to be elucidated.

Breast cancer is the most common cancer in women. Combinations of internal and external factors like as trace elements are involved in initial development of breast tumors. The aim of this study was to evaluate and compare serum levels of Zn, Cu, Se and Cu/Zn ratio in breast cancer patients and control group. This study was a descriptive cross sectional and composed of 50 women diagnosed with breast cancer and 50 normal individuals. The age range of patients and controls was between 30-50 yrs. Blood samples were obtained and serum isolated immediately. Levels of Zn, Cu and Se were measured in blood serum using atomic absorption spectrophotometry (AAS) and Graphite furnace atomic absorption spectrophotometry. Mean serum levels of Zn, Cu and Se were 0.969±.19, 1.47±.48 mg/Land 60.04±23.38μg/L, respectively, in breast cancer patients. The mean concentrations of Zn, Cu and Se serum in normal individual were 1.07±.35, 1.09± 20 mg/L and 92.42±18.70μg/L respectively. There was also a significant difference between Cu levels of patient and control group (p<0.001). In addition, the Cu/Zn ratio in breast cancer patients and controls were 1.52 and 1.12, respectively. This difference was statistically significant (p<0.001). There was a significant difference between Se levels of patients and control group (p<0.001). Based on obtained results, changes of serum level of trace elements Se, Zn and Cu could have likely biological role in the initiation or progression of breast cancer.

As one of the best known protein hormones, insulin has been recognized to play key roles in a variety of important biological process. Insulin acts on peripheral target tissues such as the adipocyte, muscle and liver to regulate glucose homeostasis. In addition to its peripheral functions, insulin and its receptor have been detected in central nervous system (CNS). Some of its effects on cognitive behaviors especially on learning and memory have been reported. Sixty male Wistar rats were divided into 6 groups randomly (n=10). All groups underwent a stereotaxic surgery and a canula was implanted in their third ventricle. Saline and different doses of Insulin (, 4,8,16 and 32 mU) were injected intracerebroventricularly. Behavioral tests carried out in Morris water maze 30 min and 24 h after injections. Our results demonstrated that the low and intermediate doses of insulin (2, 4, 8, 16 mU) showed no significant differences in escape latency and distance traveled to find hidden platform, while higher dose (32 mU) decreased these two parameters significantly. In the probe trial also those groups that received higher doses of insulin (16, 32 mu) spent more time in the target quadrant comparing with sham group. The present study suggests that intracerebroventricular administration of insulin affect memory dose dependently and higher doses improve spatial learning and memory.

Nowadays, the promotion of wound healing in some diseases and chronic disorders with the aid of herbal extracts is more challenging than ever before. That is why new compounds prepared for this purpose have been widely accepted. Echinacea purpurea has shown anti-inflammatory, immune stimulatory, fibroblastocyte stimulatory as well as anti-hyaluronidase and anti-microbial effects; therefore, it must hasten wound healing. The aim of this work was to evaluate histometrically and histopathologically the ability of dried extract ointment of Echinacea purpurea in enhancing the healing process and in reducing phlogosis of full thickness excisional skin wound in rats following topical application, compared with zinc oxide ointment by the same vehicle of eucerin. Under surgical anaesthesia, four full-thickness similar excisional wounds were made on the back of 70 rats by punching that divided into 5 groups of Echinacea purpurea 20% and 10% ointment, zinc oxide ointment, eucerin, and control. A double-blind method was employed throughout the study. All the cases were treated with topical ointments daily for 21 days. Healing process of the wounds were daily quantified and compared using digital photography and image analysis software. Histopathologic examination was performed in the 0th, 3rd, 7th, 14th, and 21st days and the wound healing was scored using healing grades I to VI regard to the wound healing parameters such as oedema & phlogistic process, congestion & haemorrhage, fibroplasia, epithelium regeneration, wound contraction, Collagen deposition and granulation tissue maturation. The overall outcome of the wound recovery for each individual group was calculated, and the results were put under a series of statistical analysis through SPSS. According to the histometric findings, the skin contraction rate in Echinacea purpurea 10% group (group II) on treatment period was much higher than that in the other groups. Also, histopathologic results revealed that overall healing rate in the group II in the second and third weeks was higher than that in the other groups (P < 0.01). Echinacea purpurea could be a new promising therapeutic approach to improve skin wound healing because of its potential anti-inflammatory and wound healing stimulatory effects.

Visceral leishmaniasis (VL) or Kala-azar caused by Leishmania infantum is a severe endemic disease in the Mediterranean basin countries including Iran. The Drugs available for treatment of VL are toxic and drug resistance is increasing in many parts of the world, thus, it is believed that vaccine development is an ideal method for prevention and control of VL. The aim of this study was to prepare recombinant P4 protein from Leishmania infantum and evaluate its immunogenicity in VL patients. DNA was extracted from Leishmania infantum and used for amplification of P4 gene by PCR. The PCR product was cloned, sequenced and expressed in E. coli using pET 28a expression vector. Recombinant P4 protein were purified and used for analysis of sera of VL patients. Analysis of the sequence of Leishmania infantum P4 gene (Li-P4) revealed that the gene consists of an ORF of 951bp with a 89% homology with P4 gene of cutaneous leishmaniasis agents. Expression of Li-P4 gene in E. coli resulted in high levels of recombinant proteins with molecular weight of 33 KD in SDS-PAGE. Immunoblotting analysis of the purified Li-P4 with sera of VL patients indicated that Li-P4 protein is a highly immunogenic protein expressed in the amastigote-stage of Leishmania infantum. This is the first study on isolation and characterization of P4 antigen from Leishmania infantum and indicates that Li-P4 protein is highly immunogenic and could be considered as a potent vaccine candidate against VL caused by Leishmania infantum.